Molecular Cancer (Aug 2020)

Comprehensive elaboration of the cGAS-STING signaling axis in cancer development and immunotherapy

  • Juyan Zheng,
  • Junluan Mo,
  • Tao Zhu,
  • Wei Zhuo,
  • Yueneng Yi,
  • Shuo Hu,
  • Jiye Yin,
  • Wei Zhang,
  • Honghao Zhou,
  • Zhaoqian Liu

DOI
https://doi.org/10.1186/s12943-020-01250-1
Journal volume & issue
Vol. 19, no. 1
pp. 1 – 19

Abstract

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Abstract Cellular recognition of microbial DNA is an evolutionarily conserved mechanism by which the innate immune system detects pathogens. Cyclic GMP-AMP synthase (cGAS) and its downstream effector, stimulator of interferon genes (STING), are involved in mediating fundamental innate antimicrobial immunity by promoting the release of type I interferons (IFNs) and other inflammatory cytokines. Accumulating evidence suggests that the activation of the cGAS-STING axis is critical for antitumor immunity. The downstream cytokines regulated by cGAS-STING, especially type I IFNs, serve as bridges connecting innate immunity with adaptive immunity. Accordingly, a growing number of studies have focused on the synthesis and screening of STING pathway agonists. However, chronic STING activation may lead to a protumor phenotype in certain malignancies. Hence, the cGAS-STING signaling pathway must be orchestrated properly when STING agonists are used alone or in combination. In this review, we discuss the dichotomous roles of the cGAS-STING pathway in tumor development and the latest advances in the use of STING agonists.

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